Is MMP-9 potent to be a new early diagnostic biomarker for dementia?

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15747
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Yokohama City University
• Principal Investigator: ABE Kie 横浜市立大学, 医学研究科, 客員研究員 (90880071)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: neurodegeneration / inflammation / biomarker / Alzheimer's disease / ADNI

Outline of Final Research Achievements

MMP-9 is attracting attention as a biomarker for early diagnosis of dementia including Alzheimer's disease (AD). In order to elucidate the activator of MMP-9 and the mechanism by which MMP-9 promotes the pathogenesis of AD, we investigated the relationship between MMP-9 and the disease progression rate of MCI patients with and without ApoEε4, a risk gene for AD. As a result, a significant correlation was observed between plasma MMP-9 concentration and dementia progression rate in ApoEε4 carriers. A correlation between MMP-9 and dementia progression was also observed in ApoEε4 non-carriers　although it was not statistically significant. It was considered that factors related to ApoE4 may be involved in adjusting the threshold and timing at which MMP-9 promotes neurodegeneration.

Free Research Field

dementia

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、MMP-9がApoEεに関連した機序によりADおよび非AD型の認知症の病態促進に関与している可能性を示唆している。
近年の研究により、MMP-9はAD患者の脳内で蓄積する異常蛋白であるtauのプロセッシングや記憶において重要な働きを担う海馬周辺の血液脳関門の障害との関連すること報告されている。
以上より、MMP-9は、認知症の早期診断に有用なバイオマーカーとしてだけでなく、認知症の病態進展のメカニズムの解明やMMP-9の不活性化による神経保護という戦略での新たな治療薬の開発にもつながる可能性がある。